Review question
To review evidence from randomized controlled trials on safety and effects of administration of buffered versus non-buffered fluids into the veins of adult patients undergoing surgery.
Background
During surgery, adults are given fluids into their veins to prevent or treat excessive loss of body water and salts (dehydration) and to compensate for loss of blood. Some fluids consist of a simple salt solution in the same salt concentration as cells and blood, such as isotonic saline; others are buffered solutions that resist changes in pH when small quantities of an acid or a base are added to them. Buffered fluids include additional electrolytes, including potassium, magnesium, and calcium, so they are matched more closely to fluid in the blood.
Study characteristics
We searched the literature up to June 2016 and found 19 studies, with a total of 1096 adults randomly assigned to receive buffered or non-buffered fluids. Some included trials involved minor surgery in otherwise fit and healthy patients. Other trials analysed outcomes after major surgery in high-risk patients, and five trials included patients undergoing renal transplant surgery. We reran the search in May 2017 and decided that we will deal with one new study of interest when we update the review.
Key results
Overall results show that the number of deaths was low and provide no evidence that choice of fluids - buffered or non-buffered - influenced the number of deaths that occurred around the time of surgery in the three trials that looked at this outcome (involving 267 participants). We found no differences between groups in the numbers of participants whose kidney function was adversely affected. Analysis of clinical outcomes suggests that buffered fluids are an equally safe and effective alternative to non-buffered fluids for adult patients undergoing surgery. The pH of the blood after surgery was reduced among patients receiving saline (pH 7.32 vs 7.38), suggesting that buffered fluids are associated with less metabolic acidosis. The saline group had higher serum chloride and sodium levels than the buffered fluid group. This might be expected, as members of the saline group were receiving saline and no other electrolytes. Higher serum chloride is a cause of metabolic acidosis.
Quality of the evidence
We assessed the quality of evidence as generally moderate, although quality of evidence showing effects of fluid choice on kidney function was low because of the presence of other factors that could affect kidney function in these participants. Evidence shows wide variation in the types of surgery performed and in drivers for and volumes of fluid administered across trials. Reported outcomes varied a great deal between included trials, and some results were expressed in ways that did not allow their inclusion in our findings.
Current evidence is insufficient to show effects of perioperative administration of buffered versus non-buffered crystalloid fluids on mortality and organ system function in adult patients following surgery. Benefits of buffered fluid were measurable in biochemical terms, particularly a significant reduction in postoperative hyperchloraemia and metabolic acidosis. Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Larger studies are needed to assess these relevant clinical outcomes.
Perioperative fluid strategies influence clinical outcomes following major surgery. Many intravenous fluid preparations are based on simple solutions, such as normal saline, that feature an electrolyte composition that differs from that of physiological plasma. Buffered fluids have a theoretical advantage of containing a substrate that acts to maintain the body’s acid-base status - typically a bicarbonate or a bicarbonate precursor such as maleate, gluconate, lactate, or acetate. Buffered fluids also provide additional electrolytes, including potassium, magnesium, and calcium, more closely matching the electrolyte balance of plasma. The putative benefits of buffered fluids have been compared with those of non-buffered fluids in the context of clinical studies conducted during the perioperative period. This review was published in 2012, and was updated in 2017.
To review effects of perioperative intravenous administration of buffered versus non-buffered fluids for plasma volume expansion or maintenance, or both, on clinical outcomes in adults undergoing all types of surgery.
We electronically searched the Clinicaltrials.gov major trials registry, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 6) in the Cochrane Library, MEDLINE (1966 to June 2016), Embase (1980 to June 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2016). We handsearched conference abstracts and, when possible, contacted leaders in the field. We reran the search in May 2017. We added one potential new study of interest to the list of ‘Studies awaiting classification' and will incorporate this trial into formal review findings when we prepare the review update.
Only randomized controlled trials that compared buffered versus non-buffered intravenous fluids for surgical patients were eligible for inclusion. We excluded other forms of comparison such as crystalloids versus colloids and colloids versus different colloids.
Two review authors screened references for eligibility, extracted data, and assessed risks of bias. We resolved disagreements by discussion and consensus, in collaboration with a third review author. We contacted trial authors to request additional information when appropriate. We presented pooled estimates for dichotomous outcomes as odds ratios (ORs) and for continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We analysed data via Review Manager 5.3 using fixed-effect models, and when heterogeneity was high (I² > 40%), we used random-effects models.
This review includes, in total, 19 publications of 18 randomized controlled trials with a total of 1096 participants. We incorporated five of those 19 studies (330 participants) after the June 2016 update. Outcome measures in the included studies were thematically similar, covering perioperative electrolyte status, renal function, and acid-base status; however, we found significant clinical and statistical heterogeneity among the included studies. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Trial authors variably reported outcome data at disparate time points and with heterogeneous patient groups. Consequently, many outcome measures are reported in small group sizes, reducing overall confidence in effect size, despite relatively low inherent bias in the included studies. Several studies reported orphan outcome measures. We did not include in the results of this review one large, ongoing study of saline versus Ringer's solution.
We found insufficient evidence on effects of fluid therapies on mortality and postoperative organ dysfunction (defined as renal insufficiency leading to renal replacement therapy); confidence intervals were wide and included both clinically relevant benefit and harm: mortality (Peto OR 1.85, 95% CI 0.37 to 9.33; I² = 0%; 3 trials, 6 deaths, 276 participants; low-quality evidence); renal insufficiency (OR 0.82, 95% CI 0.34 to 1.98; I² = 0%; 4 trials, 22 events, 276 participants; low-quality evidence).
We noted several metabolic differences, including a difference in postoperative pH measured at end of surgery of 0.05 units - lower in the non-buffered fluid group (12 studies with a total of 720 participants; 95% CI 0.04 to 0.07; I² = 61%). However, this difference was not maintained on postoperative day one. We rated the quality of evidence for this outcome as moderate. We observed a higher postoperative serum chloride level immediately after operation, with use of non-buffered fluids reported in 10 studies with a total of 530 participants (MD 6.77 mmol/L, 95% CI 3.38 to 10.17), and this difference persisted until day one postoperatively (five studies with a total of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). We rated the quality of evidence for this outcome as moderate.